tbuckley/cabot-search huggingface dataset:
Preliminary results of a phase II study of retifanlimab (PD-1 inhibitor) plus or minus epacadostat (IDO1 inhibitor) in combination with bevacizumab and hypofractionated radiotherapy for recurrent glioblastoma: NCT03532295.
Authors: Jian Li Campian, Omar H. Butt, Jiayi Huang, Jingqin Luo, Yu Tao, Roy E. Strowd, Deanna C Hissim, Sani Haider Kizilbash, Christopher Abraham, George Ansstas, Tanner Michael Johanns, Albert H. Kim, Matthew A. Ciorba, Milan G Chheda
Journal: Journal of Clinical Oncology (2022)

2058 Background: Immunotherapies targeting the programmed cell death-1 (PD-1) pathway in recurrent glioblastoma (rGBM) have failed. We hypothesize that combining therapies targeting multiple immunosuppressive pathways with cytotoxic and antiangiogenic therapies will improve survival. Here, we evaluate the safety and efficacy of an anti-PD-1 monoclonal antibody (retifanlimab), hypofractionated radiotherapy (HFRT), and bevacizumab, with or without an oral IDO1 inhibitor (epacadostat), in patients with rGBM in a nonrandomized, noncomparative sequential two-arm Phase II study. Methods: This is an open-label Phase II study of 2 sequential cohorts (Table). Cohort A first examines retifanlimab + bevacizumab + HFRT in patients with IDH1/2-WT rGBM. After a toxicity monitoring period, Cohort B, which adds epacadostat, starts enrolling. Key inclusion criteria includes dexamethasone ≤ 4 mg/day at registration and candidacy for reirradiation. Previous bevacizumab use for radiation necrosis is permitted. The primary endpoint is OS probability at 9 months (OS-9). Secondary endpoints include PFS, OS, and toxicity. Exploratory endpoints include immunological phenotyping of blood and tissue. An increase of OS-9 from 38% (bevacizumab alone) to 60% is considered clinically relevant. Results: From 6/2020 to 12/2021, we have completed accrual for cohort A and the interim analysis results are presented here: 25 patients with rGBM enrolled, with 23 evaluable. Median age is 64.3 years (42.1-81.8), 30.4% female, 30.4% MGMT promotor methylated, median KPS 90 (range 70-100), baseline dexamethasone 0 mg (range 0-4) with 52.2% of patients on dexamethasone during the first 3 cycles, median baseline ALC 1,000 cells/µl (range 300-3,700). Patients received a median of 6 cycles to date (range 2-20). Median follow-up is 11.97 months per the reverse Kaplan-Meier method. Interim analysis shows a median PFS of 9.9 months (95%CI: 5.5 to not reached (NR)) and median OS of 12.2 months (95%CI 7.3-NR). Notably, Cohort A met the primary endpoint with an OS-9 of 71.4% (95%CI: 46.7% -86.1%). No dose limiting toxicities have been yet observed. Two treatment-related grade 3 toxicities have occurred (myositis, hypertension). Cohort B enrollment is ongoing, and correlative studies pending. Conclusions: Interim analysis suggests retifanlimab combined with HFRT and bevacizumab in patients with rGBM is well-tolerated and had encouraging OS and PFS at the time of data cutoff. Cohort B, which adds epacadostat, is currently enrolling. Clinical trial information: NCT03532295. [Table: see text]
Sequential EHR-based dynamic graph network for multiple myeloma detection and feature interaction investigation.
Authors: Guanhao Wei, Li Zhou, Lynn L. Lu, Marc Romano
Journal: Journal of Clinical Oncology (2022)

e13591 Background: Electronic Health Records (EHR) provide the possibility of leveraging modern machine learning algorithms for disease detection prediction. Since a patient’s medical journey contains a complex pattern and it is difficult to identify interactive feature impacts, we propose to reconstruct patients’ attributes at different time points into dynamic graphs. Then we can use graph-based learning algorithms to enhance the predictive precision and identify leading feature interactions that reveal key services transitions. Methods: Sequential EHR like diagnosis (Dx), procedure (Px) and prescription (Rx) can be transformed into dynamic temporal graphs with nodes representing attributes, services, and medical status and edges representing patient-object interactions. Also, graph based sequential recommendation can use structured historical behavior trajectories as input, aiming to predict patient’s next behavior. Then, the model can investigate patients’ time-sensitive features interactively identifying a potential disease and then output a probability of getting that disease. Dynamic graphs can also help to track patient’s medical treatment/drug use service transitions. Results: We applied our method on a Newly Diagnosed Multiple Myeloma (NDMM) dataset consisting of 1.5 million candidates’ longitudinal medical claims from 2017 to 2020 with diagnosis rate around 0.6%. In this data set, patients’159 aggregated Dx, Rx and Px features, together with 30 demographic attributes are updated monthly. The model was trained on 4 monthly data cohorts from the 12/2017 to 03/2019 period and its performance was tested on 9 monthly cohorts from year 2020. The 1000 patients scored as having highest risk were evaluated for the predictive precision which was around 6.5% This precision compares most favorably relative to the reported 0.76% lifetime risk of getting multiple myeloma in US. We also captured the top, service transitions in NDMM patients having 30% more frequency than those in overall populations. Conclusions: The novel dynamic graph-based learning approach on a large-scale EHR dataset demonstrates the advancement of the disease detection methodology. While the outcome of this model significantly improves the accuracy of predictive precision, it also helps identify more meaningful key drivers attributing to disease. The incremental new patients identified through this novel model will provide a better basis for the evolving identification solution within Biopharma industry.
Neoadjuvant pembrolizumab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Interim results.
Authors: Weiwei Wang, Jia He, Xi Wu, Weixun Zhou, Luo Zhao, Li Li
Journal: Journal of Clinical Oncology (2022)

e16011 Background: Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in China. Its prognosis remains poor and neoadjuvant treatment may improve the prognosis for resectable ESCC. The combination of immunotherapy with cytotoxic agents has shown encouraging antitumor activity in multiple tumors but data are lacking to support this approach as a neoadjuvant strategy for locally advanced ESCC. We conducted a prospective clinical trial of pre-operative pembrolizumab with chemotherapy in patients with locally advanced ESCC. Methods: Patients with clinical stage IIB-IVA ESCC eligible for resectable surgery were prospectively enrolled. Patients received neoadjuvant pembrolizumab (200mg) and chemotherapy (docetaxel 75mg/m 2 plus cisplatin 75mg/m 2 or carboplatin area under curve 4-5) every 3 weeks for four cycles before surgery. The primary endpoint was pathologic complete response (pCR) rate and radical (R0) resection rate. Secondary endpoints include Disease Free Survival (DFS), adverse events, and the correlation between biomarkers and immunotherapy efficacy. Results: From August 2020 to January 2022, 27 eligible patients participated the study. Twenty-four patients have completed four cycles of neoadjuvant therapy, among whom 22 patients were radiologically evaluable after neoadjuvant therapy. The objective response rate (ORR) was 68.2% and disease control rate was 100%. Among 22 patients with resectable tumors, 14 patients underwent McKeown MIE and 5 patients are still waiting for the surgery. Three other patients who achieved partial response (PR) refused surgery due to fear of complications. For 14 patients who underwent esophagectomy within 29-74 (median44) days after neoadjuvant treatment, all achieved radical resection. pCR (ypT0N0) was observed in 4 patients (4/14, 28.6%). Three patients (3/14,21.4%) had a College of American Pathologists (CAP) score of 1, one (1/14, 7.1%) had a CAP of 2, and 6 (6/14, 42.9%) had a CAP of 3. Most treatment-related AEs (TRAEs) were grade 1 or 2. Grade 3/4 TRAEs of leucopenia, decreased neutrophil count and dermatitis occurred in 9 (33.3%), 14 (51.9%), and 1 (3.7%) cases, respectively. No surgical complication was observed. Conclusions: Neoadjuvant pembrolizumab plus chemotherapy has achieved satisfactory initial efficacy and safety results in locally advanced ESCC. A phase III randomized controlled trial is required to confirm the clinical benefits of this neoadjuvant therapy.
Neoadjuvent chemotherapy in rare sinonasal teratocarcinosarcoma: Long-term result from tertiary center.
Authors: Abhishek Sharma, Vijay Maruti Patil, Rahul Kumar Rai, Saswata Saha, Vanita Noronha, Nandini Sharrel Menon, Amit Joshi, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

e18005 Background: Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly aggressive disease entity having poor outcomes with available treatment modalities. Surgery followed by radiation or radical chemoradiation are considered standard therapy. However, in very locally advanced diseases surgery or radiation is not feasible and such patients are subjected to palliative therapy and have dismal outcomes. Methods: We identified 21 patients with very locally advanced SNTCS in our prospectively maintained head and neck cancer database over the last 8 years. All patients were seen in a multidisciplinary clinic prior to the start of therapy and were deemed unfit for local therapy. They were planned for 2 – 3 cycles of Neoadjuvant chemotherapy (NACT). They were then assessed in the multidisciplinary clinic for local therapy. Depending upon the response and performance status further therapy was planned. SPSS version 20 was used for the analysis. Descriptive statistics were performed and the Kaplan Meier method was used to evaluate overall survival(OS) and progression-free survival(PFS). Results: Median age was 50 years (range 27-80 Years) with male to female ratio being 6:1. ECOG PS was 0 in 3(14%), PS 1 in 14(67%) and PS 2 in 2 (9%) patients. 14 (67%) patients had Kadish C and the rest (33%) had Kadish D stage at presentation. Cisplatin &amp; Etoposide was the chemotherapy of choice for the majority of patients (14/21 patients, 67%) with Docetaxel – Cisplatin (5/21 patients,19%), and Ifosfamide – Adriamycin (2/21 patients, 9%) being the other regimens. After NACT 14/21(66%) patients underwent surgery,1/21(4%) underwent radical Chemoradiation,1/21(4%) for palliative radiation therapy and rest for best supportive care. R0 resection was achieved in 11 out of 14 (78.6%) patients. The median PFS of the study was 17.5 months (95% CI 8.2 – 26.7) and the median OS was 19 months (95% CI = 0 -47). Those who underwent surgery after NACT have achieved a median OS of 37.3 months(95% CI 0-77.7) in comparison to 6.3 months (95% CI 0.3 -12.2) for those without surgery (p value 0.02). Conclusions: NACT in very locally advanced SNTCS achieves resectability in ⅔ patients who were unresectable upfront and would have received palliative therapy. This is important as patients who undergo surgery have prolonged overall survival.
Summary of virtual tumor board platforms and implementation in neuro-oncology.
Authors: Chukwuyem Ekhator, Santosh Kesari, Ramya Tadipatri, Ekokobe Fonkem, Jai Grewal
Journal: Journal of Clinical Oncology (2022)

e13604 Background: Virtual tumor board [VTB] platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. VTBs are an emerging resource across various cancer care networks in the United States. Methods: We performed a systematic search of all VTBs incorporating a platform designed for this specific role. We reviewed Xcures, Genomet, Oncolens, Navify Tumor Board, Medical University of South Carolina [MUSC] Virtual Tumor Board, Virtual Tumor Board Tahoe Forest Cancer Center, UC Davis Health Care Center VTB and MassiveBio. Summary data examined include year of launch, demographics, characteristics of cases, average response time, advantages, and how they handle protected health information. Results: 30% of all VTBs examined launched in 2017. All had a HIPAA compliant online environment. Xcures records were reviewed where the median age of female patients was 57yrs and the median age of male patients was 55 years. The data showed that 44% (4.4 out of every 10 patients) with a confirmed treatment chose VTB integrated option. 76% of patients in Xcures registry consist primary CNS tumors. With at least 556 patients in tumor registry which included 46% Glioblastoma cases [96% primary;, 4% secondary], 13% Diffuse midline glioma with H3K27M-mutant cases, 5% Diffuse intrinsic pontine glioma cases, 3% Astrocytoma and Diffuse Astrocytoma cases, 3% Anaplastic astrocytoma cases; Glioma and Diffuse Glioma, 1% Anaplastic Oligodendroglioma cases and &lt; 1% Gliosarcoma, Oligodendroglioma, Pilocytic astrocytoma, Anaplastic pleomorphic Xanthoastrocytoma, Fibrillary astrocytoma, Oligoastrocytoma and Pleomorphic Xanthoastrocytoma cases. In the MUSC VTB, 9 neuro-oncology cases were reviewed. They meet weekly, and average response time was within 24hrs of case review.Patient demographics were not recorded. Genomet Virtual Board de-identifies all patient information; this is a virtual platform primarily focused on neuro-oncology cases. Cases involved a median of 5 specialist most commonly neuro-oncologists, neurosurgeons, radiation oncologists, molecular pathologists and neuroradiologists. Participants had an average of 23 cases reviewed. Case review revealed an age range from 6 months to 84 years [mean age 44.5 years] with 69.6% males and 30.4% females, 43.5% glioblastoma, 8.7% adenocarcinoma, 8.7% infra-tentorial tumor, &lt; 5% each: pineoblastoma, melanoma, hemangioblastoma and pilocytic astrocytoma. Average response time observed in all cases was ≤24 hours. Detailed metrics for number/percentages of brain tumor cases were not available for most other platforms at time of submission. This will be updated at presentation. Conclusions: VTBs have allowed for quicker expert analysis of cases. This has resulted in an accelerated number of cases reviewed with a shortened communication time. More studies are needed to gain additional insight into user engagement
Assessing eligibility for non-intensive chemotherapy (IC) randomized clinical trials (RCT) in patients (pts) with newly diagnosed (ND) AML from the Connect Myeloid Disease Registry.
Authors: Harry Paul Erba, Daniel Aaron Pollyea, Mikkael A. Sekeres, Guillermo Garcia-Manero, Karen Seiter, Irene DeGutis, Pavel Kiselev, Ali McBride, Edward Yu, Gail J. Roboz
Journal: Journal of Clinical Oncology (2022)

7029 Background: Pts with AML in RCTs often do not reflect the population seen in clinical practice due to strict eligibility criteria. This study evaluated criteria from a recent RCT of non-IC against a broad cohort of real-world pts with AML from the Connect ® Myeloid Disease Registry (NCT01688011). Methods: Pts were stratified into 3 groups based on the non-IC phase 3 VIALE-A trial eligibility criteria: 1) “eligible” pts who would have met all VIALE-A inclusion criteria; 2) “unfit” pts who would have been ineligible for VIALE-A due to ≥ 1 of the following: abnormal liver/kidney function, high ECOG, recent prior malignancy, comorbidities score ≥ 2 by ACE-27, hepatic grade ≥ 1, AIDS grade ≥ 1; 3) “fit” pts who would have been ineligible for VIALE-A because they would have qualified for IC (defined as: ≤ 74 y of age, low ECOG, no apparent cardiovascular/renal comorbidities, and did not meet any criteria in #2). Baseline characteristics were summarized by eligibility group. Overall survival (OS) by group was estimated using the Kaplan–Meier method. Induction regimens were categorized as IC (any regimens containing 7+3, MEC, CLAG, FLAG) or venetoclax (VEN)-based. Hazard ratios (HRs) for induction regimens among each group were estimated using Cox models adjusted for age, ELN risk, ECOG, frailty score, and comorbidity index. Results: Of 734 enrolled pts with AML (Dec 2021), most were male (61%) and white (84%); median age 71 y (range 55–97). Only 26% of pts (n = 192) were eligible for a non-IC RCT, 45% (n = 327) were ineligible due to unfitness, and 29% (n = 215) were ineligible due to overall fitness. The main reason for non-IC RCT ineligibility was high overall comorbidity grade (n = 265 [36%]). Fit pts intended to undergo transplant more often compared with unfit pts. Median OS for eligible, unfit, and fit pts were 14, 10, and 22 months, respectively. Among unfit pts, those receiving IC had significantly longer OS compared with pts receiving a VEN-based regimen (median OS 14 vs 6 months, respectively; HR: 0.51, 95% CI: 0.27–0.98, P = 0.042; Table). Eligible pts who received IC tended to have shorter median OS (13 months) vs pts who received VEN-based therapies (23 months; not sig.). Conclusions: The majority of pts with ND AML in the Registry would have been ineligible for a non-IC RCT due to being too fit or unfit. Pts ineligible for an RCT due to unfitness but who received IC maintained an OS benefit vs those receiving VEN-based therapies. This analysis suggests that non-IC RCTs may be excluding pts who appear unfit but can potentially tolerate IC and experience improved survival outcomes. Clinical trial information: NCT01688011. [Table: see text]
Characterization of genomic landscape using comprehensive circulating cell-free tumor DNA next generation sequencing in advanced thyroid carcinoma.
Authors: Valentina Tarasova, Jill Tsai, Bryan McIver, Julie E. Hallanger-Johnson, Colleen Veloski, Sarimar Agosto Salgado, Jude Masannat, Leylah Drusbosky, Christine H. Chung
Journal: Journal of Clinical Oncology (2022)

3045 Background: Availability of targeted therapies in thyroid carcinoma (TC) has challenged the conventional treatment algorithms and established urgency for timely identification of targetable genetic abnormalities. Tissue-based next generation sequencing (NGS) is often limited by tumor insufficiency and slow turn-around time. Plasma-based circulating tumor DNA (ctDNA) NGS overcomes these barriers and has been widely adopted across advanced-stage solid tumors. To date, plasma-based NGS characterization of genomic alterations in TC has not been determined. Herein, we profile potential actionable mutations detected via ctDNA in patients with advanced TC subtypes. Methods: A retrospective analysis of Guardant Health, Inc database was performed using the commercially available Guardant360 plasma-NGS test on advanced metastatic TC samples collected between 2016 and 2021. Patients with papillary TC (PTC), follicular TC (FTC), poorly differentiated TC (PDTC), medullary TC (MTC), and anaplastic TC (ATC) were clustered into four groups (G1: ATC, G2: PTC, FTC, and PDTC, G3: MTC, and G4: unspecified TC). The landscape of genetic alterations, frequencies of alterations in clinically relevant genes, and tumor mutation burden (TMB) were analyzed. Results: Of the 1,108 patients included, 47.1% were male. The median age was 65 years old (range 13-98), and 0.18% (n = 5) patients were under 18 years old. Alteration frequencies of selected, clinically relevant genes are demonstrated in the table below. TMB analysis was performed on 315 samples, and the mean TMB was higher in G1 compared to G2, G3, and G4 (p = 0.0029, 0.0826, and 0.0112, respectively). Conclusions: Plasma-based comprehensive NGS by Guardant360 may be utilized in patients with advanced metastatic TC for detecting clinically relevant genetic alterations for the selection of available targeted therapies, immunotherapy, or determination of the clinical trial eligibility. Future validation of the clinical utility by analysis of paired tumor and plasma samples is warranted. [Table: see text]
Clostridioides difficile infection in hospitalized patients with leukemia: A nationwide analysis of incidence and outcomes.
Authors: Mahmoud Mansour, Yomna Abu-Farsakh, Mohammad Darweesh, Ratib Mahfouz, Adham E. Obeidat, Ghulam Ghous, Ebubekir Daglilar
Journal: Journal of Clinical Oncology (2022)

e19042 Background: Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea. The incidence and severity of CDI have increased in adults. However, CDI has not been well studied in leukemia patients in the recent years. This study aims to evaluate incidence, mortality, and health care burden in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between Jan 1st, 2016, to Dec 31st, 2019. Using International Classification of Diseases 10th revision codes, we identified adults with a discharge diagnosis of CDI and a concomitant leukemia diagnosis. The control group included non-leukemia patients with CDI. Primary outcome was in-hospital mortality. Secondary outcomes were length of stay (LOS) and hospital charges. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 1,235,465 patients were admitted with CDI during the study period. CDI incidence per 100 discharges was higher among leukemia patients, particularly in AML and ALL patients (4.1 and 3.6, respectively) vs. 1 in general population. After adjusting for comorbidities and demographic variables, AML and ALL were independently associated with increased odds of mortality (adjusted odds ratio [AOR] 2.19 and 1.90 respectively: P &lt;0.01). Additionally, both AML and CML had significant mean increase in length of stay (7.2 and 3.1 days respectively; P &lt;0.01) and hospital charges (115,245$ and 87,198$ respectively; P &lt;0.01) compared to non-leukemia patients. Conclusions: Among leukemia patients admitted with CDI, those with AML and ALL have significantly higher adjusted odds of mortality, length of stay, and hospital charges. AML and ALL patients also had the highest incidence of CDI. Applying antibiotic stewardship and appropriately diagnosing and treating CDI is pertinent in these high-risk patients.[Table: see text]